{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T01:22:56Z","timestamp":1788744176860,"version":"build-2803163510"},"reference-count":79,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T00:00:00Z","timestamp":1634774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Rett syndrome (RTT) is a neurodevelopmental disorder with X-linked dominant inheritance caused mainly by mutations in the methyl-CpG-binding protein 2 (<jats:italic>MECP2<\/jats:italic>) gene. The effects of various <jats:italic>Mecp2<\/jats:italic> mutations have been extensively assessed in mouse models, but none adequately mimic the symptoms and pathological changes of RTT. In this study, we assessed the effects of <jats:italic>Mecp2<\/jats:italic> gene deletion on female rats (<jats:italic>Mecp2<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>) and found severe impairments in social behavior [at 8 weeks (w), 12 w, and 23 w of age], motor function [at 16 w and 26 w], and spatial cognition [at 29 w] as well as lower plasma insulin-like growth factor (but not brain-derived neurotrophic factor) and markedly reduced acetylcholine (30%\u201350%) in multiple brain regions compared to female <jats:italic>Mecp2<\/jats:italic><jats:sup>+\/+<\/jats:sup> rats [at 29 w]. Alternatively, changes in brain monoamine levels were relatively small, in contrast to reports on mouse <jats:italic>Mecp2<\/jats:italic> mutants. Female <jats:italic>Mecp2<\/jats:italic>-deficient rats express phenotypes resembling RTT and so may provide a robust model for future research on RTT pathobiology and treatment.<\/jats:p>","DOI":"10.1371\/journal.pone.0258830","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T17:58:02Z","timestamp":1634839082000},"page":"e0258830","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Substantial acetylcholine reduction in multiple brain regions of Mecp2-deficient female rats and associated behavioral abnormalities"],"prefix":"10.1371","volume":"16","author":[{"given":"Hiroyasu","family":"Murasawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Imai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiko","family":"Nagase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitomi","family":"Soumiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9279-9344","authenticated-orcid":true,"given":"Hidefumi","family":"Fukumitsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,10,21]]},"reference":[{"key":"pone.0258830.ref001","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.jpeds.2005.10.037","article-title":"Rett 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